Analgesic Effect and Action Mechanisms of Wenjing Zhitong Prescription on Primary Dysmenorrhea

Dong-ling REN; Yan-tong XU; Wei-ling WANG; Jin-ying WU; Xiao-yao LIU; Jia-lin LI; Yu-cong BI; Ting WANG

doi:10.13422/j.cnki.syfjx.20201986

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Analgesic Effect and Action Mechanisms of Wenjing Zhitong Prescription on Primary Dysmenorrhea

Pharmacology | 更新时间：2021-02-09

- Analgesic Effect and Action Mechanisms of Wenjing Zhitong Prescription on Primary Dysmenorrhea
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 3, Pages: 85-91(2021)
- 作者机构：
  
  北京中医药大学中医学院，北京中医药研究院，生命科学院，北京 100029
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20201986
  CLC： R22;R242;R2-031;R285.5
- Received：19 April 2020，
  
  Published Online：28 July 2020，
  
  Published：05 February 2021
- 稿件说明：
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任冬玲,徐砚通,王伟玲等.温经止痛方治疗原发性痛经药效学及作用机制[J].中国实验方剂学杂志,2021,27(03):85-91.

REN Dong-ling,XU Yan-tong,WANG Wei-ling,et al.Analgesic Effect and Action Mechanisms of Wenjing Zhitong Prescription on Primary Dysmenorrhea[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(03):85-91.
任冬玲,徐砚通,王伟玲等.温经止痛方治疗原发性痛经药效学及作用机制[J].中国实验方剂学杂志,2021,27(03):85-91. DOI： 10.13422/j.cnki.syfjx.20201986.

REN Dong-ling,XU Yan-tong,WANG Wei-ling,et al.Analgesic Effect and Action Mechanisms of Wenjing Zhitong Prescription on Primary Dysmenorrhea[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(03):85-91. DOI： 10.13422/j.cnki.syfjx.20201986.

摘要

目的

评价温经止痛方的镇痛效应并探索其可能的镇痛机制，为中药新药研发提供实验依据。

方法

应用缩宫素诱导大鼠扭体模型、乙酸诱导小鼠扭体模型和前列腺素E

（PGE

）诱导小鼠扭体模型，通过观察动物扭体潜伏期和扭体次数，评价温经止痛方镇痛效应。采用缩宫素诱导大鼠在体子宫平滑肌收缩和缩宫素诱导家兔的在体子宫平滑肌收缩模型，评价温经止痛方对子宫收缩频率、收缩幅度及活动力的影响。应用缩宫素诱导大鼠扭体实验模型，采用酶联免疫吸附测定法（ELISA）检测大鼠子宫组织中前列腺素F

（PGF

），前列腺素E

（PGE

）及大鼠血清中

β-

内啡肽（

-EP）的含量变化；应用实时荧光定量聚合酶链式反应（Real-time PCR）测定大鼠子宫组织中雌激素受体（ER）和缩宫素受体（OTR）表达量变化，探讨温经止痛方可能的镇痛分子机制。

结果

镇痛效应评价结果显示，缩宫素所致大鼠扭体实验中，与模型组比较，温经止痛方（1.5，3.0 g·kg

-1

）组扭体次数均明显降低（

0.05）；乙酸所致小鼠扭体实验中，与模型组比较，温经止痛方（6.0 g·kg

-1

）组小鼠的扭体反应潜伏期显著延长（

0.01），且扭体次数明显减少（

0.05）；PGE

所导致小鼠扭体实验中，与模型组比较，温经止痛方（1.5，3.0，6.0 g·kg

-1

）组的扭体次数均明显降低（

0.05，

0.01）。家兔在体子宫平滑肌实验结果，与模型组比较，温经止痛方（0.38，0.75，1.50 g·kg

-1

）组子宫平滑肌收缩频率均明显降低（

0.05，

0.01）。大鼠在体子宫平滑肌实验结果表明，与模型组比较，温经止痛方（0.75，1.50，3.00 g·kg

-1

）组收缩幅度和活动力均明显降低（

0.05）。镇痛分子机制结果证实，与模型组比较，温经止痛方（0.75，1.50，3.00 g·kg

-1

）组大鼠子宫组织中PGF

含量，PGF

/PGE

均显著降低（

0.01）；温经止痛方（3.00 g·kg

-1

）组大鼠血清中

-EP含量显著升高（

0.01）；温经止痛方（1.50，3.00 g·kg

-1

）组大鼠子宫中OTR含量明显降低（

0.05）。

结论

温经止痛方具有显著镇痛效应，其镇痛机制可能与抑制子宫平滑肌的收缩、减少PGF

含量，降低PGF

/PGE

，降低OTR在子宫组织中表达和增加血清中

-EP的含量有关。

Abstract

Objective

To evaluate the analgesic effects of Wenjing Zhitong prescription （WZP） and explore its possible analgesic mechanisms so as to provide experimental basis for research and development of new Chinese medicine.

Method

Analgesic effects of WZP were evaluated by observing the writhing latency and number in the writhing models which were induced by oxytocin in rats as well as those induced by acetic acid and prostaglandin E

（PGE

）， respectively in mice. Effect of WZP on uterine contraction frequency， amplitude and activity were evaluated by observing the oxytocin-induced contraction of uterine smooth muscle in rats and rabbits

in vivo

. In the oxytocin-induced rat writhing models， the content of prostaglandin F

（PGF

） and prostaglandin E

（PGE

） in rat uterine tissues and the content of beta-endorphins （

-EP） in rat serum were detected by enzyme-linked immunosorbent assay （ELISA）. Expression of estrogen receptor （ER） and oxytocin receptor （OTR） in rat uterine were tested by Real-time polymerase chain reaction（Real-time PCR） method to investigate the possible molecular mechanism of WZP for its analgesic effect.

Result

Results of analgesic effect showed that in oxytocin-induced rat writhing experiment， the number of writhing responses in both the WZP （1.5，3.0 g·kg

-1

） group was lower than than in the model group （

0.05）. In acetic acid-induced mice writhing experiment， the latency of writhing response in WZP （6.0 g·kg

-1

） group was significantly prolonged as compared with that in model group

（P

0.01）， and the number of writhing response was significantly reduced （

0.05）. In PGE

-induced mice writhing model， the writhing number in WZP （1.5，3.0，6.0 g·kg

-1

） groups was significantly lower than that in the model group （

0.05，

0.01）. Results of effect on uterine smooth muscle demonstrated that WZP （0.38，0.75，1.50 g·kg

-1

） could significantly reduce the frequency of uterine smooth muscle contraction in rabbits （

0.05，

0.01）， WZP （0.75，1.50，3.00 g·kg

-1

） could significantly reduce the contractile amplitude and activity of smooth muscle in the uterus of rats （

0.05）. Results of molecular mechanisms of analgesic effects showed that the WZP （0.75，1.50，3.00 g·kg

-1

） significantly reduced the content of PGF

and the ratio of PGF

to PGE

in the uterine tissue of rats （

0.01）. In the WZP （3.00 g·kg

-1

） group， the levels of

-EP in the serum of rats were significantly increased （

0.01）， and the levels of OTR in uterus of rats in the WZP （1.50，3.00 g·kg

-1

） group were significantly decreased （

0.05）.

Conclusion

Pharmacological studies demonstrated potent analgesic effect of WZP， and such analgesic effect were mediated by significantly inhibiting contraction of uterine smooth muscle， decreasing the contents of PGF

and ratio of PGF

/PGE

， reducing OTR expression in uterine as well as increasing the amount of

-EP in serum.

关键词

Keywords

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